Global InformationNGLY1 deficiency information
| NGLY1 deficiency | |
|---|---|
| Other names | NGLY1-congenital disorder of deglycosylation |
 | |
| N-glycanase 1, the affected protein | |
| Specialty | Medical genetics |
NGLY1 deficiency is a very rare genetic disorder caused by biallelic pathogenic variants in NGLY1. It is an autosomal recessive disorder. Errors in deglycosylation are responsible for the symptoms of this condition.[1] Clinically, most affected individuals display developmental delay, lack of tears, elevated liver transaminases and a movement disorder.[2] NGLY1 deficiency is difficult to diagnose, and most individuals have been identified by exome sequencing.
NGLY1 deficiency causes a dysfunction in the endoplasmic reticulum-associated degradation pathway. NGLY1 encodes an enzyme, N-glycanase 1, that cleaves N-glycans. Without N-glycanase, N-glycosylated proteins that are misfolded in the endoplasmic reticulum cannot be degraded, and thus accumulate in the cytoplasm of cells.[3][4]
- ^ Online Mendelian Inheritance in Man (OMIM): CONGENITAL DISORDER OF DEGLYCOSYLATION; CDDG - 615273
- ^ Lam C, Wolfe L, Need A, Shashi V, Enns G (February 2018). "NGLY1-Related Congenital Disorder of Deglycosylation". In Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A, Lam C, Wolfe L, Need A, Shashi V, Enns G (eds.). GeneReviews. Seattle (WA): University of Washington, Seattle. PMID 29419975.
- ^ Freeze HH (March 2013). "Understanding human glycosylation disorders: biochemistry leads the charge". The Journal of Biological Chemistry. 288 (10): 6936–45. doi:10.1074/jbc.R112.429274. PMC 3591604. PMID 23329837.
- ^ Enns GM, Shashi V, Bainbridge M, Gambello MJ, Zahir FR, Bast T, et al. (October 2014). "Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway". Genetics in Medicine. 16 (10): 751–8. doi:10.1038/gim.2014.22. PMC 4243708. PMID 24651605.